表观遗传识别动机的β-hairpin模型的分子动力学
Xiange Zheng1, Chuanjie Wu, Jay W Ponder
1Department of Chemistry and of Biochemistry, Washington University, St. Louis, Missouri 63105, United States.
Journal of the American Chemical Society
|September 1, 2012
概括
氨酸甲基化通过降低溶解成本,提高分子识别,增加β-hairpin稳定性. 在模拟中,AMOEBA力场准确地预测这些效应,在模拟中表现优于其他效应.
科学领域:
- 计算化学计算化学
- 生物物理学的生物物理.
- 分子动力学模拟模型
背景情况:
- 在蛋白质折叠和分子识别中,β-hairpin结构至关重要.
- 氨酸甲基化与表观遗传修饰有关,并影响蛋白质相互作用.
- 了解-π和芳香相互作用是特征分子识别的关键.
研究的目的:
- 通过计算来研究氨酸甲基化对β-毛形状和稳定性的影响.
- 评估在观察到的NMR光谱差异中,阴离子-π,溶解和芳香相互作用的作用.
- 与其他模型相比,评估AMOEBA力场在模拟甲基化的准确性.
主要方法:
- 具有不同程度的lysine ε-甲基化的β-hairpin模型的实验性表征.
- 开发和验证使用AMOEBA力场对e-甲基化胺的独立参数化.
- 在显式溶剂中对四种模型 (n=0,1,2,3) 的100ns分子动力学模拟.
主要成果:
- 随着lysine的e-甲基化,β-hairpin的稳定性显著增加,这与实验数据一致.
- 对于所有,AMOEBA力场正确预测了超过80%的观察到的核过度修复效应 (NOE).
- 基于断的力场 (AMBER,CHARMM,OPLSAA) 对NOE的预测准确性明显较低.
结论:
- 甲基化组的解溶自由能量降低补偿了减少的阴离子-π 相互作用.
- AMOEBA力场准确地捕捉了氨酸甲基化对β-hairpin稳定性和动态的影响.
- 使用先进力场的计算模拟对于理解复杂的分子识别事件至关重要.
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